Potential role of the ABCG2-Q141K polymorphism in type 2 diabetes

PLoS One. 2021 Dec 2;16(12):e0260957. doi: 10.1371/journal.pone.0260957. eCollection 2021.

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease and variations in multispecific membrane transporter functions may affect T2DM development, complications or treatment. In this work we have analyzed the potential effects of a major polymorphism, the Q141K variant of the ABCG2 transporter in T2DM. The ABCG2 protein is a multispecific xeno- and endobiotic transporter, affecting drug metabolism and playing a key role in uric acid extrusion. The ABCG2-Q141K variant, with reduced expression level and function, is present in 15-35% of individuals, depending on the genetic background of the population, and has been shown to significantly affect gout development. Several other diseases, including hypertension, chronic renal failure, and T2DM have also been reported to be associated with high serum uric acid levels, suggesting that ABCG2 may also play a role in these conditions. In this work we have compared relatively small cohorts (n = 203) of T2DM patients (n = 99) and healthy (n = 104) individuals regarding the major laboratory indicators of T2DM and determined the presence of the SNP rs2231142 (C421A), resulting the ABCG2-Q141K protein variant. We found significantly higher blood glucose and HbA1c levels in the T2DM patients carrying the ABCG2-Q141K variant. These findings may emphasize the potential metabolic role of ABCG2 in T2DM and indicate that further research should explore how prevention and treatment of this disease may be affected by the frequent polymorphism of ABCG2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Prognosis

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins

Grants and funding

This study has been supported by grants from Hungarian National Development and Innovation Office (NKFIH K-128011 to V.Gy.), FIEK_16-1-2016-0005 (B.S), and VEKOP-2.1.1-15-2016-00117. The employer of the author J.Cs. did not have a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.